Research Design and Methods
The biographer extracts glucose through the skin by reverse iontophoresis and measures the extracted sample using an electrochemical biosensor. Iontophoresis is a technique whereby a low-level electric current (0.3 mA/cm2 in these studies) is passed through the skin between an anode and a cathode . The current is carried primarily by the migration of sodium ions toward the cathode. Uncharged molecules (e.g., glucose) are carried along by convective transport (electroosmosis) [7,8]. The amount of glucose extracted at the cathode has been demonstrated to correlate with blood glucose in diabetic subjects . In the biographer, the extracted glucose is measured by an amperometric biosensor using detection of H2O2 generated by the glucose/glucose oxidase reaction. The operating principles of the biosensor are described elsewhere [10,11,12].
The biographer provides readings every 20 min after calibration using a fingerstick blood glucose measurement taken after a 3-h equilibration period. This single-point calibration, which accounts for variability in both biosensor sensitivity and skin permeability, is used to convert subsequent biosensor measurements into glucose readings. A signal-processing algorithm  is programmed into the biographer software. The reading lags behind the corresponding blood glucose value by ~17 min.
Data integrity screens in the biographer software detect spurious data points resulting from such sources as electrical noise, high background currents, and open or short circuits. The presence of data points not conforming to objective a priori criteria results in the disregarding (or skipping) of a glucose reading. The biographer also contains skin temperature and skin conductance sensors. The latter is directly related to the amount of sweat on the surface of the skin. Because large temperature changes or the presence of glucose in sweat can confound the glucose measurement, once the output from either of these sensors exceeds a predetermined threshold, the measurement for that cycle will be skipped. These data-screening methods thus prevent potentially inaccurate glucose readings. In the studies presented here, ~20% of all readings were skipped because of data integrity screens.
Four clinical studies were performed, each with institutional review board approval. Accuracy was evaluated in a controlled clinic setting, a simulated home environment, and the home environment. An additional laboratory method comparison study evaluated accuracy versus a laboratory standard method (YSI analyzer; Yellow Springs Instruments). Biographer readings were compared to serial capillary blood glucose measurements performed with a variety of instruments. Subjects wore the biographer for 15-h sessions (3-h equilibration and 12-h measurement periods). In the clinic setting, glucose levels were manipulated to produce periods of hypoglycemia and hyperglycemia. All subjects were adults (18 years of age and older) with type 1 or type 2 diabetes requiring insulin treatment. The biographer readings were masked from the patients and investigators during the study period. All dose adjustments for insulin were completed using blood glucose measurements. The table summarizes the design of the clinical studies along with the number of biographer uses and paired points. Patient diaries were used to record the times of meals and insulin injections. The diaries did not require the subjects to record symptoms of possible hypoglycemia.
Data download and analyses of accuracy and precision are described elsewhere [2,3,4]. The objective of this analysis was to evaluate the ability of the biographer to correctly detect hypoglycemia as determined by the comparative blood glucose value. This analysis was completed by defining hypoglycemia as blood glucose 3.9 mmol/l and varying the biographer low-glucose alert level. At each alert level, each biographer reading was evaluated as either a true positive (TP), false positive (FP), true negative (TN), or a false negative (FN). The definitions of each of the terms are as follows:
Hypoglycemic event: blood glucose 3.9 mmol/l
Biographer low-glucose alert level: threshold below which the biographer would trigger the audible alarm
TP: blood glucose 3.9 mmol/l and biographer less than or equal to the low alert level
FP: blood glucose >3.9 mmol/l but biographer less than or equal to the low alert level
TN: blood glucose >3.9 mmol/l and biographer more than the low alert level
FN: blood glucose 3.9 mmol/l but biographer more than the low alert level
Sensitivity and specificity were defined by the following equations and determined at seven low-glucose alert levels (3.9, 4.4, 5.0, 5.6, 6.1, 6.7, and 7.2 mmol/l).These results were then used to prepare the ROC curves. The TPF is the same as the sensitivity and reflects the frequency with which the biographer correctly identified hypoglycemia of all occasions in which the blood glucose test result was 3.9 mmol/l. The FPF is calculated by subtracting the specificity from 1.0. The FPF reflects the frequency with which the biographer incorrectly identified hypoglycemia of all occasions in which the blood glucose test result was >3.9 mmol/l. Two types of hypoglycemic events were analyzed. First, only paired biographer readings and blood glucose values were analyzed. For this paired-point analysis, the comparative blood glucose result must have been obtained in the time period between 10 and 20 min before the biographer reading. The results of all studies were analyzed in this manner. In addition, the home-environment data were analyzed for all blood glucose 3.9 mmol/l, even if there were no paired biographer readings. This was completed by evaluating biographer readings immediately surrounding the hypoglycemic event.
Diabetes Care. 2001;24(5) © 2001 American Diabetes Association, Inc.
Cite this: Detection of Hypoglycemia With the GlucoWatch Biographer - Medscape - May 15, 2001.